Systemic sclerosis: an update.
Systemic sclerosis (SSc) is a complex and heterogeneous chronic illness characterized by substantial patient to patient variability in clinical manifestations, internal organ involvement, and outcome. Genetic factors contribute to disease susceptibility, but environmental influences also play a significant role. The pathogenesis of SSc encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations and morbidity and must be addressed in the treatment plan. Although vascular interventions appear to reduce the frequency and severity of complications, such as scleroderma renal crisis and pulmonary hypertension, current therapies generally target the immune component of SSc in a non-selective fashion and have largely failed as diseases-modifying interventions. Newer insights into the mechanisms underlying autoimmunity, vascular injury and destruction, and particularly tissue fibrosis provide novel potential targets for therapy. Transforming growth factor-ss is a ubiquitous cytokine that appears to contribute to fibroblast activation, collagen overproduction, and pathological tissue fibrosis. Neutralizing antibodies and small molecules that block TGF-beta activation or function are effective in shutting down TGF-beta signaling and selectively inhibit the progression of fibrosis and may be entering clinical trials for the treatment of SSc.
Varga
John
J
Northwest University, Feinberg School of Medicine, Chicago, Illinois, USA. j-varga@northwestern.edu
D001808:Blood Vessels / Q000473:pathology; D002317:Cardiovascular Agents / Q000627:therapeutic use; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000209:etiology; D007674:Kidney Diseases / Q000209:etiology; D017563:Lung Diseases, Interstitial / Q000209:etiology; D011928:Raynaud Disease / Q000209:etiology; D012595:Scleroderma, Systemic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome
D002317:Cardiovascular Agents; D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta